Betulin silver nanoparticles qualify as efficient antimelanoma agents in in vitro and in vivo studies

被引:28
作者
Danciu, Corina [1 ]
Pinzaru, Iulia [1 ]
Coricovac, Dorina [1 ]
Andrica, Florina [1 ]
Sizemore, Ioana [2 ]
Dehelean, Cristina [1 ]
Baderca, Flavia [3 ]
Lazureanu, Voichita [3 ]
Soica, Codruta [1 ]
Mioc, Marius [1 ]
Radeke, Heinfried [4 ]
机构
[1] Victor Babes Univ Med & Pharm, Fac Pharm, 2nd Eftimie Murgu Sq, Timisoara 300041, Romania
[2] Wright State Univ, Dept Chem, Dayton, OH 45435 USA
[3] Victor Babes Univ Med & Pharm, Fac Med, 2nd Eftimie Murgu Sq, Timisoara 300041, Romania
[4] Goethe Univ Frankfurt Main, Inst Pharmacol & Toxicol Clin, D-60590 Frankfurt, Germany
关键词
Betulin silver nanoparticles; Melanoma; C57BL/6J mice; Histopathological assessment; B16; melanoma; 4A5; B16Ova; CELLULAR UPTAKE; ANIMAL-MODELS; CELLS; PROLIFERATION; COMBINATION; CARCINOMA; APOPTOSIS; THERAPY; ENHANCE; KERATINOCYTES;
D O I
10.1016/j.ejpb.2018.11.006
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The current study was purported to assess the: (1) in vitro toxicity of betulin silver nanoparticles (AgNPs-B), bare and capped with polyethylene glycol (PEG), on two murine melanoma cell lines (B164A5 and B160va) and on healthy cell lines (keratinocytes and melanocytes), and (ii) in vivo antitumor efficacy of PEGylated AgNPs-B in an experimental melanoma model. Bare and PEG-capped AgNPs-B were synthesized by a chemical reduction method resulting in stable and non-aggregated spherical AgNPs-B and PEG-AgNPs-B, of narrow size distributions and mean hydrodynamic diameters of 25 nm and 75 nm, respectively. In vitro assessments were achieved by MTT and Annexin V-FITC assays and in vivo evaluation involved non-invasive techniques for the surveillance of the physiological skin parameters changes and histopathological examination of the harvested organs. The in vitro results revealed selective cytotoxicity against melanoma cells, at low doses that are nontoxic to normal cells; higher doses were associated with the loss of selectivity and toxicity for healthy cells. PEGylated formulation of betulin exerted a dose-dependent pro-apoptotic effect, more obvious in the case of B164A5 cells. Histopathological analysis suggested that PEGylated AgNPs-B developed relevant in vivo effects as antimelanoma agents by decreasing the tumor volume and inhibiting the development of secondary tumors.
引用
收藏
页码:1 / 19
页数:19
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